# Regulation and Function of Intermediate Filaments in Cell Mechanics

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2020 · $1,771,683

## Abstract

The overall hypothesis of this P01 Grant is that the unique properties of vimentin intermediate filaments (VIF)
play a key role in regulating cytoskeletal organization and modulate the micromechanical properties of cells as
well as a diverse set of cellular activities, including cell polarization, cell migration, or tissue morphogenesis.
The Project Investigators and Core Leaders are all leaders in the field of cell biology and cell mechanics. Over
the past funding period collaborative studies have established unique cell reagents and assays leading to key
insights into the properties and functions of VIF. These insights provide a strong foundation for this renewal
application. In preparation of this application further preliminary results have been collected supporting the
feasibility of each of the projects. The projects are interactive conceptually, technically and programmatically,
making the aggregate of the projects much greater than the sum of its parts. In Project #1, Dr. Goldman,
Northwestern University, will determine the structural interactions among VIF, microtubules (MT) and actin
microfilaments (MF) using high resolution microscopic techniques; determine the role of the assembly and
disassembly of VIF in wound healing and motility assays; and determine the role of VIF phosphorylation in
cellular signal transduction. In Project #2, Dr. Gelfand, Northwestern University will determine the dynamic
mechanisms regulating VIF-MT interactions; determine the mechanisms responsible for the dynamic
interactions between VIF and MF; and determine how VIF modulate the transport and distribution of
membrane-bound organelles. In Project #3, Dr. Danuser, UTSW Dallas, will examine mechanisms by which
VIF control MT organization and cell polarity; investigate mechanisms by which VIF control cell traction; and
examine mechanisms by which VIF respond to cell-external guidance cues. In Project #4, Dr. Weitz, Harvard
University, will determine the properties of reconstituted networks of VIF as well as composite networks
comprised either of VIF, MF and myosin motors, or VIF, MT and their associated motors; study the
micromechanical properties of VIF networks in living cells in 3D settings and in reconstituted networks derived
from these cells. In Project #5, Dr. Janmey, University of Pennsylvania, will determine the mechanisms that
regulate force-dependent VIF assembly in cells; study the mechanics of VIF networks under compression in
vitro; and determine how VIF regulate the response of cells and tissues to compression loading. Interactions
among members of all projects and data sharing will allow for integration of physical characterizations made by
different groups using methods unique to their labs that cover a wide range of time and length scales. These
efforts will be supported by the Cell and Tissue Core which, under the guidance of Dr. Ridge, Northwestern
University, will support all PIs by maintaining the required WT and vimentin null mouse models...

## Key facts

- **NIH application ID:** 9994763
- **Project number:** 5P01GM096971-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Gaudenz Danuser
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,771,683
- **Award type:** 5
- **Project period:** 2011-06-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994763

## Citation

> US National Institutes of Health, RePORTER application 9994763, Regulation and Function of Intermediate Filaments in Cell Mechanics (5P01GM096971-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994763. Licensed CC0.

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